Development of a novel passive sampler based on a combination of membrane assisted solvent extraction and molecularly imprinted polymer for monitoring of selected pharmaceuticals in surface waters

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Pharmaceuticals are an important group of persistent emerging pollutants due to being continuously detected in the aquatic environment. Pharmaceuticals are compounds whose therapeutic effects enhance the health of individuals. However, these compounds have the potential to enter the environment as part of effluents from wastewater treatment plants while other sources include improper disposal of expired and unused medication and human excreta. Although these pollutants exist in trace levels (µg L-1 to ng L-1 ) in environmental samples, they have gained a lot of attention in the science community owing to the perceived detrimental effects on human health and ecotoxicological effects in aquatic life. As such, determination of pharmaceuticals in the environment has become an essential component in environmental monitoring studies. Various analytical techniques have been reported mainly grab sampling followed by solid phase extraction being the most reported. However, the challenge has been that these pharmaceuticals exist in trace levels which requires extremely sensitive approaches. At the same time, they exist as mixtures which requires the need for analytical methods which allows for multi-residue analysis at a time. One of the obvious choices of sampling is grab sampling that involves instantaneous collection of samples. The main challenge of such is that this requires large amounts of samples as well as potential to miss the episodic events of pollution. In this regard, recent studies now advocate for passive sampler-based approaches where a sorbent is deployed in the environment over a period of time. This allows for estimation of time-weighted average (TWA) concentrations which caters for episodic events of pollution. In this regard, the purpose of the current study was to develop an alternative passive sampling technique based on a combination of a molecularly imprinted polymer (MIP) sorbent and membrane assisted solvent extraction (MASE) for the determination of pharmaceuticals belonging to five different classes in surface water. The approach was to synthesize a smart polymer using molecular imprinting technology, place it inside a semi-permeable polypropylene membrane and finally place it in a protective chamber. The chamber and its content, now referred to as the passive sampler was then deployed under optimized conditions for monitoring of the five model pharmaceuticals belonging to different groups. The first part of the work involved synthesizing a smart polymer, the MIP for efficient and selective extraction of pharmaceuticals belonging to different groups. This was done by selecting an appropriate template for molecular imprinting process. Cavity tuning experiments which involved the utilization of all the target pharmaceuticals whether as single or multi-template were conducted. The venlafaxine imprinted polymer was successfully selected based on its cross-selectivity for the selected pharmaceuticals. The synthesized polymer attained maximum matrix-matched adsorption capacities ranging from 206 to 418 ng mg-1 for individual pharmaceuticals within 80 min. Batch adsorption and kinetic studies indicated that the binding of the selected pharmaceuticals on the MIP particles resulted in multiple interactions through chemisorption. An analytical method for determination of the target pharmaceuticals was successfully developed using liquid chromatography-mass spectrometry (LC-MS), giving detection limits ranging from 0.03 to 0.31 ng mL-1 and quantification limits ranging from 0.12 - 3.81 ng mL-1 for individual pharmaceuticals. The venlafaxine imprinted polymer was further applied as a selective sorbent for solid phase extraction of an antiretroviral (nevirapine), an antidepressant (venlafaxine), a muscle relaxant (methocarbamol), an anticonvulsant (carbamazepine) and a cardiac stimulant (etilefrine) in dam water samples, yielding recoveries ranging from 43 - 69%. This preliminary data indicated that MIP cross selectivity can be an essential and attractive approach in the monitoring of organic pollutants belonging to different classes in environmental water bodies. This work, presented as Paper 1 in the thesis was published in Polymer Bulletin Journal. The synthesized venlafaxine imprinted smart polymer was then used in combination with a membrane assisted solvent extraction technique, referred to as MASE-MIP for the extraction of these compounds in complex environmental water samples. The MASE-MIP combination utilized the cross-selectivity of the synthesized venlafaxine viii MIP whilst preventing co-extraction of larger molecules to yield cleaner extracts and increased selectivity. After efficient extraction, the sample extracts were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LCqTOF/MS). The MASE-MIP was optimized for various significant experimental parameters such as the influence of the sample salt content, the stirring rate, the stirring time and the amount of MIP using a central composite design. Optimum extraction conditions for a sample volume of 18 mL were found to be 5 g of salt content, a stirring rate of 400 rpm, an extraction time of 60 min and 50 mg of MIP, yielding good extraction efficiencies ranging from 38 – 91% for individual pharmaceuticals. The optimized MASE-MIP-LC-qTOF/MS method yielded detection limits in the range of 0.09 to 0.20 ng mL-1 and quantification limits ranging from 0.31 to 0.69 ng mL-1 for individual pharmaceuticals. Furthermore, the optimized extraction method was applied in environmental monitoring of selected pharmaceuticals in two important rivers in South Africa. All selected model compounds were detected in the water samples at concentrations ranging from 0.19 to 2.48 ng mL-1 . This illustrated emphasis of a need to continuously monitor the presence of these compounds in environmental waters. The monitoring could be done through the proposed analytical method which has proven to be precise and accurate. This work, presented as Paper 2 in this thesis has been published in Chemosphere journal. The developed MASE-MIP technique was further used in combination with the passive sampling technique to form a MASE-MIP based passive sampler for extraction and monitoring of selected pharmaceuticals in environmental water bodies. This technique utilized the cross-selectivity of the synthesized MIP, the size exclusion and protective membrane and allowed for preconcentration of the target pharmaceuticals into the green receiver solvent (ionic liquid). The passive sampler approach was based on allowing the targeted compounds to diffuse selectively in an integrative manner through the polypropylene membrane which housed an ionic liquid as a green receiving solvent and a MIP. Upon successful diffusion, the analytes were selectively adsorbed by a MIP. The technique was optimized for parameters such as effects of biofouling, ix deployment time and solvent type for the receiver phase. Furthermore, the passive sampler was calibrated in laboratory-based experiments to obtain sampling rates (Rs) for each target pharmaceutical with the view to attain estimated time weighted average (TWA) concentrations of the targeted pharmaceuticals in environmental waters. The optimum matrix-matched sampling rates obtained ranged from 0.0007 - 0.0018 L d-1 for individual pharmaceuticals, whilst the method detection and quantification limits ranged from 2.45 - 3.26 ng L-1 and 8.06 - 10.81 ng L-1 , respectively. Upon deployment in a dam situated in a highly populated township in South Africa, only etilefrine and methocarbamol were detected and quantified at maximum TWA concentrations of 12.88 and 72.29 ng L-1 , respectively. This work is well presented as Paper 3 in this thesis. Paper 3 is a manuscript under review in Water Research journal. The MASE-MIP based passive sampler showed proven ability to selectively extract targeted pharmaceuticals prior to their determination using LC-qTOF/MS. In this case, the presented experimental procedures allow for detection of trace level environmental concentrations of the targeted pharmaceuticals, making them suitable alternative analytical methods that can be utilized for monitoring of these compounds in environmental water bodies.
A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Science, University of the Witwatersrand, 2022
Novel passive sampler, Membrane assisted solvent extraction, Molecularly imprinted polymer, Pharmaceuticals